Germline PKHD1 mutations are protective against colorectal cancer |
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Authors: | Christopher J Ward Yanhong Wu Ruth A Johnson John R Woollard Eric J Bergstralh Mine S Cicek Jason Bakeberg Sandro Rossetti Christina M Heyer Gloria M Petersen Noralene M Lindor Stephen N Thibodeau Peter C Harris Vicente E Torres Marie C Hogan Lisa A Boardman |
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Institution: | Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. ward.christopher@mayo.edu |
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Abstract: | The autosomal recessive polycystic kidney disease (ARPKD) gene, PKHD1, has been implicated in the genesis or growth of colorectal adenocarcinoma, as a high level of somatic mutations was found in colorectal tumor tissue. To determine whether carriers of a single PKHD1 mutation are at increased risk of colorectal carcinoma, we assessed the prevalence of the commonest European mutation, T36M. First, we assayed a European cohort of ARPKD patients and found T36M was responsible for 13.1% of mutations. We then investigated two European cohorts with colorectal adenocarcinoma versus two control cohorts of similar age and gender. Screening for the most common PKHD1 mutation, T36M, we detected 15:3,603 (0.42%) controls versus 1:3,767 (0.027%) colorectal cancer individuals, indicating that heterozygous PKHD1 mutations are not a risk factor and are protective (p=0.0002). We also show that the carriage rate for PKHD1 mutations in the European population is higher than previous accepted at 3.2% (1:31 genomes). |
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